{
  "abstract": "Tumour-host crosstalk is an emerging hallmark of malignancy. It is increasingly recognised that cancer alters non-tumour bearing distant organs, with important consequences for disease progression and survival. Skeletal muscle loss, a defining feature of cancer-associated cachexia, contributes to morbidity and reduced quality of life, yet its underlying mechanisms remain poorly understood. In this study we analysed the secretome of pancreatic cancer cells and identified a metabolite-driven signal that induces myotube atrophy. Our data suggests that atrophy, which seems to involve cytoskeletal stress and increased myosin contractility, arises from cancer cell-dependent reductive metabolic rewiring. Pancreatic cancer cells conditioned their environment with elevated levels of lactate, generating a lactate-rich extracellular milieu that decrease the NAD+/NADH ratio in myotubes. This redox imbalance impaired oxidative metabolism, decreasing -ketoglutarate (KG) levels and disrupted KG-dependent processes. Restoration of NAD+ or KG levels rescued myotube atrophy. Skeletal muscle from cancer-associated cachexia mouse models exhibited reduced KG levels. Collectively, these findings identify a targetable metabolite-mediated mechanism of tumour-muscle crosstalk.",
  "abstract_shown": true,
  "affiliations": [
    "The Francis Crick Insitute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "V. Papalazarou"
    },
    {
      "name": "J. Coomes"
    },
    {
      "name": "L. Rossi"
    },
    {
      "name": "V. M. Lionello"
    },
    {
      "name": "I. Furlani"
    },
    {
      "name": "F. S. Tedesco"
    },
    {
      "affs": [
        0
      ],
      "name": "K. Vousden"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ec55kw47m6qcw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.15.759464",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759464v1.full",
  "id": "ec55kw47m6qcw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759464v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7222540825",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759464v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ec55kw47m6qcw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:11Z",
      "native_id": "10.64898/2026.10.15.759464",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759464v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "NAD+ limitation and α-ketoglutarate depletion define cancer induced muscle atrophy",
  "title_text": "NAD+ limitation and α-ketoglutarate depletion define cancer induced muscle atrophy",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:11Z",
  "url": "https://research.draconitic.com/paper/ec55kw47m6qcw",
  "venue": "bioRxiv",
  "versions": []
}